Despite a decline in the incidence of Sudden Infant Death Syndrome (SIDS) over the past several years, this tragic syndrome remains the leading cause of infant deaths between 1 month and 1 year of age. The long- term objectives of this proposal are to elucidate physiologic mechanisms that underlie SIDS and to develop age-appropriate, non-invasive tests that will identify infants who are at greatest risk for SIDS. These tests focus on peripheral and central mechanisms involved in the integrated control of cardiac, BP, and respiratory function. Because epidemiologic data suggest that risk for SIDS is influenced by the quality of the prenatal environment, the studies start with measurements made during late gestation. Assessments then continue through infancy to determine physiologic changes that coincide with the period of maximal risk for SIDS. Subjects are the fetuses and infants of mothers from a low-SES population in New York City and from a rural Native American population on the Pine Ridge Reservation in South Dakota. The infants born on this reservation are 3-4 times more likely to die of SIDS than the US population as a whole. Studies begin during gestation with measures of fetal heart rate and fetal movement and the coupling between movement and changes in heart rate. In newborn, two and twelve month old infants, the focus is on heart rate, several indices of heart rate variability, blood pressure, peripheral blood flow, respiratory rate, and electro-cortical activity utilizing a high-density (128 lead) EEG monitor. Measures of infant physiology are collected during extended baseline periods and during the challenge of head-up tilting. The proposed studies are shaped by the hypothesis that some SIDS are due to failure in autonomic control and focus on effects of five known risk factors: age, prone sleeping, maternal smoking and alcohol consumption during pregnancy, genetic polymorphisms of the serotonin transporter promoter (the "long" allele increases risk for SIDS), and warm environmental temperatures. Relevance to public health: the overall goals of this grant are to understand the mechanisms that underlie Sudden Infant Death Syndrome and other neurobehavioral disorders and to develop tests that will assess risk as early as possible in the infant's life.